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Nat Commun ; 10(1): 2835, 2019 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-31249377

RESUMEN

During embryogenesis cells make fate decisions within complex tissue environments. The levels and dynamics of transcription factor expression regulate these decisions. Here, we use single cell live imaging of an endogenous HES5 reporter and absolute protein quantification to gain a dynamic view of neurogenesis in the embryonic mammalian spinal cord. We report that dividing neural progenitors show both aperiodic and periodic HES5 protein fluctuations. Mathematical modelling suggests that in progenitor cells the HES5 oscillator operates close to its bifurcation boundary where stochastic conversions between dynamics are possible. HES5 expression becomes more frequently periodic as cells transition to differentiation which, coupled with an overall decline in HES5 expression, creates a transient period of oscillations with higher fold expression change. This increases the decoding capacity of HES5 oscillations and correlates with interneuron versus motor neuron cell fate. Thus, HES5 undergoes complex changes in gene expression dynamics as cells differentiate.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Células-Madre Neurales/metabolismo , Neurogénesis , Proteínas Represoras/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/química , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones/embriología , Ratones/metabolismo , Ratones Endogámicos ICR , Ratones Noqueados , Células-Madre Neurales/química , Células-Madre Neurales/citología , Proteínas Represoras/química , Proteínas Represoras/genética , Análisis de la Célula Individual
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